Conversion between sirolimus and everolimus in heart transplant recipients

Sirolimus and everolimus are mechanistic target of rapamycin inhibitors (mTORi) that may be included in immunosuppression regimens for orthotopic heart transplant (OHT) recipients. mTORi play a role in slowing progression of cardiac allograft vasculopathy; however, they have poor tolerability, sometimes necessitating a change between agents or therapies. The literature surrounding a conversion between mTORi are incongruent, thus this study was designed to assess the concentration/dose ratio for each medication around the time of conversion to provide guidance for a conversion strategy between mTORi.

We conducted a retrospective study of adult OHT recipients who were maintained on both sirolimus- and everolimus-based immunosuppression regimens. The primary outcome was the concentration/dose (C/d) ratio of sirolimus to everolimus. Secondary outcomes included changes in hematologic and lipid labs and patient-reported intolerances.

The C/d ratio of sirolimus was 4.42, whereas the everolimus ratio was 2.23, resulting in a sirolimus: everolimus ratio of 1.98. Secondarily, after converting between mTORi, 93% of patients who reported intolerance(s) to one agent had a resolution of that intolerance. In our patient population, everolimus appeared better tolerated than sirolimus, with significantly more patients having no reported intolerances and significantly fewer patients experiencing edema. Other lab values were similar between patients receiving sirolimus and everolimus, except for an increased hemoglobin level in those receiving everolimus.

The conversion ratio of 1:2 observed in our population suggests OHT recipients may require an increased dose of EVL compared with SRL to maintain the same goal trough levels. A conversion between mTORi appeared to improve tolerability and did not lead to clinically significant worsening of any measured lab value.